Once-a-Year Bone Drug Lowers Fracture Risk

Reclast even caused death rate to fall in older users, study finds

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TUESDAY, Sept. 18, 2007 (HealthDay News) -- One annual injection of the drug zoledronic acid (Reclast) not only reduces the number of new hip fractures for older users, it can also save their lives.

So finds the first trial to show an improvement in mortality for the drug. Previous studies had shown a reduced risk of fracture and improved bone density in patients with osteoporosis but not such a boost in outcomes.

"We changed the fracture rate and, when we analyzed the data, we had a significant mortality reduction. We never dreamed we'd have that," said study author Dr. Kenneth W. Lyles. He spoke from Honolulu, where he is presenting the data at the American Society of Bone and Mineral Research annual meeting.

The study was released early by the New England Journal of Medicine to coincide with the presentation.

Lyles is professor of medicine and vice chairman for clinical research in the department of medicine at Duke University Medical Center in Durham, N.C.

Novartis Pharma, which manufactures Reclast, funded the study. Lyles also has ties with the company.

"This is the first test of using this to prevent further fractures in elderly patients, and the reason that is a big deal is people weren't sure if zoledronic acid inhibited osteoclasts [cells] which are needed for repair" of the initial fracture, explained Paul Brandt, an associate professor of neuroscience and experimental therapeutics with the Texas A&M Health Science Center College of Medicine.

"This study shows that it doesn't interfere with that process and does give the beneficial effect of reducing further fracture rates," said Brandt, who was not involved in the trial.

An estimated 345,000 Americans are hospitalized each year with a hip fracture, and as the Baby Boomers age, that number is certain to grow.

According to an accompanying editorial, 36 percent of patients who have sustained a hip fracture will die within two years of the incident. These individuals are also five to 10 times more likely to suffer another hip fracture.

Many such fractures are the result of osteoporosis, a disease which primarily affects women in their postmenopausal years. With this disease, bones thin out and become more fragile, causing them to break more easily. Fracture can often result in severe disability, even death.

Reclast was approved in August by the U.S. Food and Drug Administration to treat osteoporosis in postmenopausal women.

The drug is a bisphosphonate, a class of drugs which also includes Fosamax, Actonel and Boniva. These medications -- the most commonly used treatments for osteoporosis -- work by slowing the body's natural reabsorption of bone.

While the drugs are effective, there has been a problem with getting patients to take them as they should.

For this study, more than 2,100 men and women were randomized to receive Reclast or a placebo within 90 days after surgery for a hip fracture. Participants were followed for an average of almost two years.

Almost 14 percent of those not taking Reclast suffered a new fracture, the researchers found, compared with only 8.6 percent of those taking the drug. Also, 13.3 percent of patients not taking Reclast died, versus 9.6 percent of those taking the drug.

In the end, patients taking Reclast were 28 percent less likely to die and 35 percent less likely to have another fracture than those on placebo.

Bone mineral density also increased in the Reclast group, the team reported.

It seems likely that the decline in mortality was due at least in part to the decline in fractures, the authors stated.

Only 43 percent of participants were classified as having osteoporosis but most likely had some weakening of the bone. "What's happening here is that you have a thinning of the bone that isn't being detected by a scan," Brandt said.

There were some concerns about the design of the trial. For example, patients in the placebo arm did not receive another medication, although many did receive bone-boosting vitamin D. However, the authors noted that the patients enrolled in this trial could not or would not take an oral bisphosphonate.

Patients taking Reclast will also need to take vitamin D and calcium, they added, and some will experience flu-like symptoms which can be alleviated with a nonsteroidal anti-inflammatory drug.

"This appears to be the most potent of the bisphosphonates. It reduced bone turnover more and had a significant effect on fracture rate. The once-a-year dose obviously is attractive," said Dr. Stephen Honig, director of the Osteoporosis Center at the New York University Hospital for Joint Diseases. "This combination makes it potentially a very important drug. The caveat is the potential side effects. Other studies have found atrial fibrillation."

However, unlike one previous trial, the researchers on this study found no differences in reports of the irregular heartbeat known as atrial fibrillation between the two groups. They also found no reports of osteonecrosis of the jaw, a painful jaw condition, which had previously been associated with this class of drugs.